Hydrochloric Acid → 2-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (295b) (230 mg, 0.44 mmol) and LiOH monohydrate (Sigma-Aldrich) (184 mg, 4.38 mmol) in dioxane (1.5 mL) and water (0.75 mL). The reaction mixture was heated at 110° C. for 17 h. After cooling to RT, the reaction mixture was diluted with Et2O and water and the layers were separated. The Et2O layer was discarded. The aq. layer was acidified with 2 M HCl and extracted with EtOAc (3×). The combined EtOAc layers were dried over anhydrous Na2SO4, filtered and concentrated to give a light yellow solid. m/z (ESI, +ve) 498.2 (M+H)+. The light yellow solid was dissolved in 1 mL of dioxane and treated with 4.0 M HCl in 1,4-dioxane (Sigma-Aldrich) (5 mL, 20.00 mmol) at RT. After 24 h, the reaction mixture was concentrated and the orange solid was collected by filtration to give 2-(1-aminocyclopropyl)-5-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid hydrochloride (295c) (180 mg, 0.42 mmol, 95% yield). m/z (ESI, +ve) 381.1 (M−NH2)+.

Provenance & Evidence